Analyte Sensors and Methods of Use

ABSTRACT

Analyte sensors for determining the concentration of an analyte in a sample. The sensors have a sample chamber having an inlet with a projection extending from an edge of the sensor for facilitating flow of sample into the sample chamber.

FIELD OF THE INVENTION

This invention relates to analytical sensors for the detection ofanalyte in a sample, and methods of making and using the sensors.

BACKGROUND

Biosensors, also referred to as analytical sensors or merely sensors,are commonly used to determine the presence and concentration of abiological analyte in a sample. Such biosensors are used, for example,to monitor blood glucose levels in diabetic patients.

As sensors continue to be used, there continues to be an interest insensors that are easy to manufacture and easy for a patient to use.

SUMMARY

The present disclosure provides sensors and methods for the detectionand quantification of an analyte in a sample. The sensors have an inletto the sample chamber that facilitates drawing of sample (e.g., blood)into the chamber. The sensors include an element that provides an openpath to the sample chamber and that inhibits restriction of the inlet bythe patient's skin.

In general, certain embodiments of the invention include sensors foranalysis of an analyte in a sample, e.g., a small volume sample, by, forexample, coulometry, amperometry and/or potentiometry. The sensorsinclude at least a working electrode and a counter electrode, which maybe on the same substrate (e.g., co-planar) or may be on differentsubstrates (e.g., facing). Sensing chemistry may be present on theelectrode(s). The sensors also include a sample chamber to hold thesample in electrolytic contact with the working electrode. An inlet,present in an edge of the sensor, provides fluid communication to thesample chamber. The sensors may be configured for side-filling ortip-filling. In addition, in some embodiments, the sensor may be part ofan integrated sample acquisition and analyte measurement device. Anintegrated sample acquisition and analyte measurement device may includea sensor and a skin piercing member, so that the device can be used topierce the skin of a user to cause flow of a fluid sample, such asblood, that may then be collected by the sensor.

In one particular aspect, the disclosure is directed to an analytesensor for determining the concentration of an analyte in a sample, thesensor comprising a sample chamber having an inlet with a width and anelement such as projection extending from an edge of the sensor, theprojection having a height and a width. The width of the projection maybe the same or more than the inlet width, or may be less than the inletwidth, e.g., no more than about 80% of the inlet width, e.g., no morethan about 75% or about 50% of the inlet width. The average projectionwidth may be no more than about 50% of the inlet width, or no more thanabout 40%. The height of the projection may be at least about 0.1 mm orat least about 0.2 mm. The projection may extend from a side edge of thesubstrate or from an end edge of the substrate. In some embodiments, thesensor includes a second projection.

In another particular aspect, the disclosure is directed to an analytesensor having a first substrate, a second substrate, and a spacer layertherebetween, with a sample chamber defined between the first substrateand the second substrate bounded by the spacer layer. The sample chamberhas at least one inlet, and a protrusion extending from the firstsubstrate at the inlet. The sensor may include second, third and/orfourth protrusions.

In yet another particular aspect, the disclosure is directed to ananalyte sensor for determining the concentration of an analyte in asample, the sensor having a first substrate and a second substrate eachhaving a first side edge and a second side edge, a sample chamberdefined between the first substrate and the second substrate, with thesample chamber extending from the first side edge to the second sideedge, a first aperture and a second aperture between the first substrateand the second substrate at the first side edge and the second sideedge, respectively, and a first projection and a second projectionextending from the first side edge of the first substrate and the secondside edge of the first substrate, respectively, proximate the apertures,each of the projections having a width less than the width of theproximate aperture. The sensor may additional have a third projectionand a fourth projection extending from the first side edge of the secondsubstrate and the second side edge of the second substrate,respectively, proximate the apertures. The maximum width of theprojection may be no more than about 80% of the aperture width, e.g., nomore than about 75% or about 50% of the aperture width. The averageprojection width may be no more than about 50% of the inlet width, or nomore than about 40%. The height of the projections may be at least about0.1 mm or at least about 0.2 mm.

The sensors may have a sample chamber volume of no more than about 1microliter, and in some embodiments, a volume of no more than about 0.5microliter.

Methods of using the sensors include determining the concentration ofglucose.

These and various other features which characterize the invention arepointed out with particularity in the attached claims. For a betterunderstanding of the invention, its advantages, and objectives obtainedby its use, reference should be made to the drawings and to theaccompanying description, in which there is illustrated and describedpreferred embodiments of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Referring now to the drawings, wherein like reference numerals andletters indicate corresponding structure throughout the several views:

FIG. 1A is a schematic perspective view of a first embodiment of asensor strip in accordance with the present invention;

FIG. 1B is an exploded view of the sensor strip of FIG. 1A, the layersillustrated individually with the electrodes in a first configuration;

FIG. 2A is a schematic view of a second embodiment of a sensor strip inaccordance with the present invention;

FIG. 2B is an exploded view of the sensor strip of FIG. 2A, the layersillustrated individually with the electrodes in a second configuration;

FIG. 3A is a schematic top view of a third embodiment of a sensor stripin accordance with the present invention;

FIG. 3B is a schematic top view of a fourth embodiment of a sensor stripin accordance with the present invention; and

FIG. 4 is an enlarged top plan view of a portion of a sensor stripaccording to the present invention.

DETAILED DESCRIPTION

This disclosure provides sensors and methods of making and using thosesensors that facilitate the drawing of fluid sample (e.g., blood) intothe sensor by inhibiting contact of the patient's skin with the sampleinlet.

Referring to the Drawings in general and FIGS. 1A and 1B in particular,a first embodiment of a sensor 10 is schematically illustrated, hereinshown in the shape of a strip. It is to be understood that the sensormay be any suitable shape. Sensor strip 10 has a first substrate 12, asecond substrate 14, and a spacer 15 positioned therebetween. Sensorstrip 10 is a layered construction.

Sensor strip 10 includes at least one working electrode 22 and at leastone counter electrode 24. Although not illustrated, sensor strip 10 mayalso include an optional fill indicator electrode and/or and optionalinsertion monitor.

Sensor strip 10 has a first, distal end 10A and an opposite, proximalend 10B. At distal end 10A, sample to be analyzed is applied to sensor10. Distal end 10A could be referred as ‘the fill end’, ‘samplereceiving end’, or similar. Proximal end 10B of sensor 10 is configuredfor operable, and usually releasable, connecting to a device such as ameter. Sensor strip 10, in certain embodiments, has a generallyrectangular shape, i.e., its length is longer than its width, althoughother shapes 10 are possible as well, as noted above. Sensor strip 10has four edges, end edge 16 at distal end 10A, end edge 18 at proximalend 10, and side edges 17, 19 extending therebetween.

The dimensions of a sensor may vary. In certain embodiments, the overalllength of sensor strip 10, from end edge 16 to end edge 18, may be noless than about 10 mm and no greater than about 50 mm. For example, thelength may be between about 30 and 45 mm; e.g., about 30 to 40 mm. It isunderstood, however that shorter and longer sensor strips 10 could bemade. In certain embodiments, the overall width of sensor strip 10, fromside edge 17 to side edge 19, may be no less than about 3 mm and nogreater than about 15 mm. For example, the width may be between about 4and 10 mm, about 5 to 8 mm, or about 5 to 6 mm. In one particularexample, sensor strip 10 has a length of about 32 mm and a width ofabout 6 mm. In another particular example, sensor strip 10 has a lengthof about 40 mm and a width of about 5 mm. In yet another particularexample, sensor strip 10 has a length of about 34 mm and a width ofabout 5 mm.

The sensor includes a sample chamber for receiving a volume of sample tobe analyzed; in the embodiment illustrated, particularly in FIG. 1A,sensor strip 10 includes sample chamber 20 having an inlet 21 for accessto sample chamber 20. In the embodiment illustrated, sensor strip 10 isa side-fill sensor strip, having inlet 21 present on side edge 17 ofstrip 10. In this embodiment, sensor strip 10 has a second inlet at sideedge 19 (not seen). Tip-fill sensors, having an inlet at, for example,end edge 16, are also within the scope of this disclosure, as well ascorner fill sensors.

Proximate inlet 21, sensor strip 10 includes an element for facilitatingthe drawing of fluid sample (e.g., blood) into sensor strip 10 byinhibiting contact of the patient's skin with sample inlet 21. Sensorstrip 10 includes a projection 30 extending outward from at least one ofsubstrates 12, 14 in the location of inlet 21. In this embodiment,projection 30 is present on both substrates, substrate 12 and substrate14, and on both side edges, edge 17 and edge 19. Additional discussionof projection 30 is provided below. In some embodiments, the element(e.g., projection 30) may facilitate the drawing of fluid sample (e.g.,blood) into sensor strip 10 by capillary fluid flow mechanism.

Referring to FIGS. 2A and 2B, an alternate embodiment of a sensor isillustrated as sensor strip 110. Similar to sensor strip 10, sensorstrip 110 has a first substrate 112, a second substrate 114, and aspacer 115 positioned therebetween. Sensor strip 110 includes at leastone working electrode 122 and at least one counter electrode 124, inthis embodiment, both on substrate 114.

Sensor strip 110 has a first, distal end 110A and an opposite, proximalend 110B. At distal end 110A, sample to be analyzed is applied to sensor110. Distal end 110A could be referred as ‘the fill end’, ‘samplereceiving end’, or similar. Proximal end 110B of sensor 110 isconfigured for operable, and preferably releasable, connecting to adevice such as a meter. Similar to sensor strip 10, sensor strip 110 isa layered construction, in certain embodiments having a generallyrectangular shape, which is formed by first and second substrates 112,114 and defined by end edges 116, 118 and side edges 117, 119. Thediscussion above about substrates 12, 14 and spacer 15 and the variousfeatures applies to substrates 112, 114 and spacer 115 and the variousfeatures.

Similar to sample chamber 20 of sensor strip 10, sensor strip 110includes sample chamber 120 defined by substrate 112, substrate 114 andspacer 115. Sample chamber 120 includes an inlet 121 for access tosample chamber 120. Sensor strip 110 is a tip-fill sensor, having inlet121 in end edge 116 at end 110A. Extending from sample chamber 120,through substrate 112, is a vent 125. The discussion above about samplechamber 20 and its measurement zone also applies to sample chamber 120.

Proximate inlet 121, sensor strip 110 includes an element forfacilitating the drawing of fluid sample (e.g., blood) into sensor strip110 by inhibiting contact of the patient's skin with sample inlet 121.Sensor strip 110 includes a projection 130 extending outward from atleast one of substrates 112, 114 in the location of inlet 121. In thisembodiment, projection 130 is present on only one substrate, substrate112. Additional discussion of projection 130 is provided below.

Referring to FIGS. 3A and 3B, two other alternate embodiments of sensorsare illustrated as sensor strips 210, 210′, respectively. Similar tosensor strips 10, 110 discussed before, sensor strips 210, 210′ have afirst substrate, a second substrate, and a spacer positionedtherebetween. Sensor strips 210, 210′ include at least one workingelectrode and at least one counter electrode.

Sensor strips 210, 210′ have a first, distal end 210A, 210A′ and anopposite, proximal end 210B, 210B′. Similar to sensor strips 10, 110,sensor strips 210, 210′ are layered constructions, in this embodiment,having a generally rectangular shape with a width at proximal end 210B,210B′ and a reduced width closer to distal end 210A, 210A′. The shape ofsensor strip 210, 210′ is defined by end edges 216, 216′, 218, 218′ andside edges 217, 217′, 219, 219′. Each of side edges 217, 217′, 219, 219′has a first portion where edges 217A, 217A′, 219A, 219A′ are recessed orreduced (e.g., the sensor width is reduced in the first portion) ascompared to a second portion, defined by edges 217B, 217B′, 219B, 218B′,where the width is the entire width of the sensor.

Edges 217A, 217A′, 219A, 219A′ in the first portion may have generallyany shape, such as linear, arcuate (e.g., concave or convex), orirregular. Sections of the portion may have side edges 217A, 217A′,219A, 219A′ angled (e.g., tapered) or parallel to each other. Strip 210,of FIG. 3A, has non-parallel, arcuate edges 217A, 219A in the firstportion, whereas strip 210′ of FIG. 3B has generally parallel, generallylinear edges 217A′, 219A′, having an arcuate transition region proximateedges 217B′, 219B′. Having a recessed or reduced portion, such asdefined by edges 217A, 217A′, 219A, 219A′, facilitates differentiatingdistal end 210A, 210A′ from proximal end 210B, 210B′.

Similar to the previous sensor embodiments, sensor strips 210, 210′include a sample chamber 220, 220′ defined by the substrates and thespacer. Sample chambers 220, 220′ include an inlet 221, 221′ for accessthereto. Sensor strips 210, 210′ are side-fill sensors, having twoinlets 221, 221′, one in edge 217A, 217A′ and one in edge 219A, 219A′proximate end 210A, 210A′.

Proximate inlet 221, 221′, sensor strips 210, 210′ include an elementfor facilitating the drawing of fluid sample (e.g., blood) into sensorstrips 210, 210′ by inhibiting contact of the patient's skin with sampleinlet 221, 221′. Sensor strips 210, 210′ include a projection 230, 230′extending outward from at least one of substrates in the location ofinlet 221, 221′. In this embodiment, projection 230, 230′ is present ononly one substrate, substrate, at both inlets 221. Additional discussionof projection 230, 230′ is provided below.

The following detailed discussion applies to both sensor strip 10 andsensor strips 110, 210, 210′ and their various elements and features.Although the following discussion usually uses the references numeralsfor sensor strip 10 (e.g., substrates 12, 14, sample chamber 20, inlet21, etc.), it is to be understood that this discussion applies to bothembodiments, i.e., sensor strip 10, sensor strip 110 and sensor strips210, 210′.

Substrates and Spacer

As provided above, sensor strip 10 has first and second substrates 12,14, non-conducting, inert substrates which form the overall shape andsize of sensor strip 10. The substrates may be substantially rigid orsubstantially flexible. In certain embodiments, the substrates areflexible or deformable. Examples of suitable materials for thesubstrates include, but are not limited, to polyester, polyethylene,polycarbonate, polypropylene, nylon, and other “plastics” or polymers.In certain embodiments the substrate material is “Melinex” polyester.Other non-conducting materials may also be used.

As indicated above, positioned between substrate 12 and substrate 14 maybe spacer 15 to separate first substrate 12 from second substrate 14. Insome embodiments, spacer 15 extends from end 10A to end 10B of thesensor strip, or extends short of one or both ends. The spacer is aninert non-conducting substrate, typically at least as flexible anddeformable (or as rigid) as the substrates. In certain embodiments, thespacer is an adhesive layer or double-sided adhesive tape or film thatis continuous and contiguous. Any adhesive selected for the spacershould be selected to not diffuse or release material which mayinterfere with accurate analyte measurement.

In certain embodiments, the thickness of the spacer may be constantthroughout, and may be at least about 0.01 mm (10 μm) and no greaterthan about 1 mm or about 0.5 mm. For example, the thickness may bebetween about 0.02 mm (20 μm) and about 0.2 mm (200 μm). In one certainembodiment, the thickness is about 0.05 mm (50 μm), and about 0.1 mm(100 μm) in another embodiment.

Sample Chamber

The sensor includes a sample chamber for receiving a volume of sample tobe analyzed; access to the sample chamber is provided via an inlet. Thesample chamber is configured so that when a sample is provided in thechamber, the sample is in electrolytic contact with both a workingelectrode and a counter electrode, which allows electrical current toflow between the electrodes to effect the electrolysis (electrooxidationor electroreduction) of the analyte.

Sample chamber 20 is defined by substrate 12, substrate 14 and spacer15; in many embodiments, sample chamber 20 exists between substrate 12and substrate 14 where spacer 15 is not present. Typically, a portion ofthe spacer is removed to provide a volume between the substrates withoutthe spacer; this volume of removed spacer is the sample chamber. Forembodiments that include a spacer between the substrates, the thicknessof the sample chamber is generally the thickness of the spacer.

The sample chamber has a volume sufficient to receive a sample ofbiological fluid therein. In some embodiments, such as when a sensor isa small volume sensor, the sample chamber has a volume that is typicallyno more than about for example no more than about 0.5 μL and also forexample, no more than about 0.25 μL. A volume of no more than about 0.1μL is also suitable for the sample chamber, as are volumes of no morethan about 0.05 μL and about 0.03 μL.

A measurement zone is contained within the sample chamber and is theregion of the sample chamber that contains only that portion of thesample that is interrogated during the analyte assay. In some designs,the measurement zone has a volume that is approximately equal to thevolume of the sample chamber. In some embodiments the measurement zoneincludes 80% of the sample chamber, 90% in other embodiments, and about100% in yet other embodiments.

As provided above, the thickness of the sample chamber correspondstypically to the thickness of any spacer. Particularly for facingelectrode configurations, as in the sensor illustrated in FIG. 1B, thisthickness is small to promote rapid electrolysis of the analyte, as moreof the sample will be in contact with the electrode surface for a givensample volume. In addition, a thin sample chamber helps to reduce errorsfrom diffusion of analyte into the measurement zone from other portionsof the sample chamber during the analyte assay, because diffusion timeis long relative to the measurement time, which may be about 5 secondsor less.

Electrodes

The sensor includes a working electrode and at least one counterelectrode. The counter electrode may be a counter/reference electrode.If multiple counter electrodes are present, one of the counterelectrodes will be a counter electrode and one or more may be referenceelectrodes.

For sensor 10, at least one working electrode is positioned on one offirst substrate 12 and second substrate 14 in the measurement zoneand/or sample chamber. In FIG. 1B, working electrode 22 is illustratedon substrate 12. Working electrode 22 extends from the sample chamber20, proximate distal end 10A, to the other end of the sensor 10, end10B, as an electrode extension called a “trace”. The trace provides acontact pad for providing electrical connection to a meter or otherdevice to allow for data and measurement collection.

For sensor 110, at least one working electrode is positioned on one offirst substrate 112 and second substrate 114 in the measurement zoneand/or sample chamber. In FIG. 2B, working electrode 122 is illustratedon substrate 114. Working electrode 122 extends from the sample chamber,proximate distal end 110A, to the other end of the sensor 110, end 110B,as an electrode extension called a “trace”. The trace provides a contactpad for providing electrical connection to a meter or other device toallow for data and measurement collection.

Working electrode 22, 122 may be a layer of conductive material such asgold, carbon, platinum, ruthenium dioxide, palladium, or othernon-corroding, conducting material. The working electrode may be acombination of two or more conductive materials. An example of asuitable conductive epoxy is ECCOCOAT CT5079-3 Carbon-Filled ConductiveEpoxy Coating (available from W.R. Grace Company, Woburn, Mass.). Thematerial of the working electrode typically has relatively lowelectrical resistance and is typically electrochemically inert over thepotential range of the sensor during operation.

The working electrode may be applied on the substrate by any of variousmethods, including by being deposited, such as by vapor deposition orvacuum deposition or otherwise sputtered, printed on a flat surface orin an embossed or otherwise recessed surface, transferred from aseparate carrier or liner, etched, or molded. Suitable methods ofprinting include screen-printing, piezoelectric printing, ink jetprinting, laser printing, photolithography, and painting.

The sensor also includes at least one counter electrode positionedwithin the measurement zone and/or sample chamber. In FIG. 1B, counterelectrode 24 is illustrated on substrate 14. Counter electrode 24extends from the sample chamber 20, proximate first end 10A, to theother end of the sensor 10, end 10B, as an electrode extension called a“trace”. The trace provides a contact pad for providing electricalconnection to a meter or other device to allow for data and measurementcollection. In FIG. 2B, counter electrode 124 is illustrated onsubstrate 114. Counter electrode 124 extends from the sample chamber,proximate first end 110A, to the other end of the sensor 110, end 110B,as an electrode extension called a “trace”. The trace provides a contactpad for providing electrical connection to a meter or other device toallow for data and measurement collection.

Counter electrodes 24, 124 may be constructed in a manner similar toworking electrodes 22, 122. Suitable materials for the counter/referenceor reference electrode include Ag/AgCl or Ag/AgBr on a non-conductingbase material or silver chloride on a silver metal base. The samematerials and methods may be used for the counter electrode as areavailable for the working electrode, although different materials andmethods may also be used. The counter electrode may include a mix ofmultiple conducting materials, such as Ag/AgCl and carbon.

The working electrode and counter electrode may be positioned oppositeto and facing each other to form facing electrodes. See for example,FIG. 1B, which has working electrode 22 on substrate 12 and counterelectrode 24 on substrate 14, forming facing electrodes. In thisconfiguration, the sample chamber is typically present between the twoelectrodes 22, 24. In other embodiments, the working electrode andcounter electrode may be positioned generally planar to one another,such as on the same substrate, to form co-planar or planar electrodes.See for example, FIG. 2B, which has both working electrode 122 andcounter electrode 124 on substrate 114, forming planar electrodes.

In some instances, it is desirable to be able to determine when thesample chamber of the sensor is sufficiently filled with sample. Sensorstrip 10 may be indicated as filled, or substantially filled, byobserving a signal between an optional indicator (or fill) electrode andone or both of working electrode 22 or counter electrode 24 as samplechamber 20 fills with fluid. When fluid reaches the indicator electrode,the signal from that electrode will change. Suitable signals forobserving include, for example, voltage, current, resistance, impedance,or capacitance between the indicator electrode and, for example, workingelectrode 22. Alternatively, the sensor may be observed after filling todetermine if a value of the signal (e.g., voltage, current, resistance,impedance, or capacitance) has been reached indicating that the samplechamber is filled.

For side-fill sensors, such as sensor 10 of FIGS. 1A and 1B and sensor210 of FIG. 3, an indicator electrode may be present on each side of thecounter electrode. This permits the user to fill the sample chamber fromeither the left or right side with an indicator electrode disposedfurther upstream. This three-electrode configuration is not necessary.Side-fill sensors may also have a single indicator electrode and mayinclude some indication as to which side should be placed in contactwith the sample fluid.

The indicator electrode may also be used to improve the precision of theanalyte measurements. The indicator electrode may operate as a workingelectrode or as a counter electrode or counter/reference electrode.Measurements from the indicator electrode/working electrode may becombined (e.g., added or averaged) with those from the firstcounter/reference electrode/working electrode to obtain more accuratemeasurements.

The sensor or equipment that the sensor connected is with (e.g., ameter) may include a signal (e.g., a visual sign or auditory tone) thatis activated in response to activation of the indicator electrode toalert the user that the desired zone has been filled. The sensor orequipment may be configured to initiate a reading when the indicatorelectrode indicates that the measurement zone has been filled with orwithout alerting the user. The reading may be initiated, for example, byapplying a potential between the working electrode and the counterelectrode and beginning to monitor the signals generated at the workingelectrode.

Sensing Chemistry

In addition to working electrode 22, sensing chemistry material(s) arepreferably provided in sample chamber 20 for the analysis of theanalyte. Sensing chemistry material facilitates the transfer ofelectrons between working electrode 22 and the analyte in the sample.Any sensing chemistry may be used in the sensor; the sensing chemistrymay include one or more materials.

The sensing chemistry may be diffusible or leachable, or non-diffusibleor non-leachable. For purposes of discussion herein, the term“diffusible” will be used to represent “diffusible or leachable” and theterm “non-diffusible” will be used to represent “non-diffusible ornon-leachable” and variations thereof. Placement of sensing chemistrycomponents may depend on whether they are diffusible or not. Forexample, both non-diffusible and/or diffusible component(s) may form asensing layer on the working electrode. Alternatively, one or morediffusible components may be present on any surface in the samplechamber prior to the introduction of the sample to be analyzed. Asanother example, one or more diffusible component(s) may be placed inthe sample prior to introduction of the sample into the sample chamber.

The sensing chemistry generally includes an electron transfer agent thatfacilitates the transfer of electrons to or from the analyte. Theelectron transfer agent may be diffusible or non-diffusible, and may bepresent on working electrode 22 as a layer. One example of a suitableelectron transfer agent is an enzyme which catalyzes a reaction of theanalyte. For example, a glucose oxidase or glucose dehydrogenase, suchas pyrroloquinoline quinone glucose dehydrogenase (PQQ), is used whenthe analyte is glucose. Other enzymes may be used for other analytes.

The electron transfer agent, whether it is diffusible or not,facilitates a current between the working electrode and the analyte andenables the electrochemical analysis of molecules. The agent facilitatesthe transfer electrons between the electrode and the analyte.

This sensing chemistry may, additionally to or alternatively to theelectron transfer agent, include a redox mediator. Certain embodimentsuse a redox mediator that is a transition metal compound or complex.Examples of suitable transition metal compounds or complexes includeosmium, ruthenium, iron, and cobalt compounds or complexes. In thesecomplexes, the transition metal is coordinatively bound to one or moreligands, which are typically mono-, di-, tri-, or tetradentate. Theredox mediator may be a polymeric redox mediator or a redox polymer(i.e., a polymer having one or more redox species). Examples of suitableredox mediators and redox polymers are disclosed in U.S. Pat. No.6,338,790, for example, and in U.S. Pat. Nos. 6,605,200 and 6,605,201.

If the redox mediator is non-diffusible, then the redox mediator may bepresent on the working electrode as a layer. In an embodiment having aredox mediator and an electron transfer agent, if the redox mediator andelectron transfer agent are both non-leachable, then both components areon the working electrode as individual layers, or combined and appliedas a single layer.

The redox mediator, whether diffusible or not, mediates a currentbetween the working electrode and the analyte and enables theelectrochemical analysis of molecules which may not be suited for directelectrochemical reaction on an electrode. The mediator functions as anagent to transfer electrons between the electrode and the analyte.

In accordance with this disclosure, sensors, such as sensor strips 10,110, 210, 210′ include projection 30, 130, 230, 230′ for facilitatingthe drawing of fluid sample (e.g., blood) into the sensor by inhibitingcontact of the patient's skin with the sample inlet. Projection 30 is anelement extending outward from at least one of substrates 12, 14 in thelocation of sample chamber inlet 21. Projection 30 extends out from theedge in which the inlet is present. For example, projection 30 extendsout from edge 17 and edge 19 of both substrates 12, 14; projection 130extends out from edge 116 of substrate 112; and projections 230, 230′extend out from edges 217A, 217A′, 219A, 219A′.

Referring to FIG. 4, a generic projection is illustrated. This may beprojection 30 extending from edge 17 or from edge 19, projection 130extending from edge 116, projection 230 extending from edge 217A or edge219A, or projection 230′ extending from edge 217A′ or edge 219A′.However to facilitate discussion, the projection in FIG. 4 will bereferred to as projection 30 ending from edge 17, although it should beunderstood that the project and edge could be any of those describedherein. Similarly, to facilitate discussion, the inlet will be referredto as inlet 21.

Projection 30 extends from edge 17 at inlet 21. Projection 30 may beadditionally or alternately referred to as an outward notch, aprotrusion, an overhang, a cantilever, a tab, or other similar term thatdescribes an element extending out from the sensor. Projection 30inhibits blocking or sealing of inlet 21 by the skin of the sensor user.The small, protrusion of projection 30 out from edge 17 inhibits theuser's skin from blocking the inlet and maintains a passage between theskin and inlet 21 for fluid sample to flow to the sample chamber.Additionally, projection 30 may function as a visual and/or tactileindicator to the user as to the location of inlet 21.

For layered sensors, such as sensor strips 10, 110, 210, projection 30can be present on both substrates (e.g., substrates 12, 14) or only onesubstrate.

The shape and size of projection 30 is selected so that the user's skincannot readily conform around projection 30, thus blocking access toinlet 21 between the substrates.

Projection 30 has a width W, measured in the same direction as a width Xof inlet 21. In this embodiment, inlet 21 has the same width X as itssample chamber. In some embodiments, projection 30 may extend over theentire width X of inlet 21; i.e., width W is the same or more than widthX. In other embodiments however, the maximum width W of projection 30 isless than width X of inlet 21, and in this embodiment, less than thewidth of the sample chamber. It is understood that in some embodiments,the width of the sample chamber may be greater or smaller than width Xof inlet 21. The maximum width W of projection 30, in some embodiment,is no more than 80% of width X of inlet 21, often no more than 75%. Insome embodiments, the maximum width W is no more than 70% of width X. Inother embodiments, the maximum width W is no more than 60% of width X.In still other embodiments, the maximum width W is no more than 50% ofthe width X of inlet 21. In other embodiments, the average width W ofprojection 30 is no more than 50% of width X. For example, the averagewidth W is no more than 45% of width X, and in some embodiments no morethan 40% of width X. In some embodiments, maximum width W is no morethan about 1.5 mm, e.g., no more than about 1 mm, e.g., no more thanabout 0.5 mm.

Projection 30 also has a height, the distance from side edge 17 thatprojection 30 extends. Height H of projection 30 is at least 0.1 mm,often at least 0.2 mm, e.g., at least 0.3 mm. Typically, the larger theheight H, the better the passage created due to projection 30.

The ratio of width W to height H, in some embodiments, is about 2:1 toabout 1:2. In other embodiments, the ratio of width W to height H isabout 1.5:1 to about 1:1.5.

In the illustrated embodiment of FIG. 4, projection 30 has a triangularshape, with its base even with edge 17 and its apex pointing away frominlet 21. In some embodiments, the apex may be defined by a radius.Other configurations for projection 30 are suitable, such as rectangular(including square), arcuate (e.g., semi-circular), pentagon, etc.Geometric shapes could have arcuate sides; for example, a substantiallytriangular or triangular-like projection could have arcuate (e.g.,concave or convex) sides; other shapes could additionally have arcuateside(s). Projection 30 may be symmetrical or unsymmetrical. In someembodiments, however, projection 30 has an apex or point extending awayfrom inlet 21; the apex may have a radius associate with it. Geometricshapes such as triangles, pentagons, etc., have an apex. A configurationsuch as projection 30 provides a small area (e.g., a point) forcontacting the skin of the sensor user.

In some embodiments, the extension or cantilever of projection 30 outfrom edge 17 facilitates drawing of sample into inlet 21 and the samplechamber. Details regarding using a cantilevered sensor for facilitatingsample flow are discussed in co-pending application Ser. No. 11/237,447filed Sep. 27, 2005.

In one particular exemplary embodiment, a triangular projection 30 has aheight H of about 0.38 mm (15 mil) and a width W of about 0.5 mm (20mil), whereas inlet 21 has a width X of about 1 mm (40 mil). In thisembodiment, projection 30 has a width that is about 50% of the inletwidth. The ratio of width W to height H is 4:3, or, about 1.33:1.

Various specific configurations of sensors having projections areillustrated in U.S. Design patent application Ser. No. ______ (attorneydocket 12008.103US01), the entire disclosure of which is incorporatedherein by reference.

General Method for Manufacturing Sensors

Sensor strips 10, 110, 210, 210′ discussed above, are sandwiched orlayered constructions having substrates 12, 14, 112, 114 spaced apart,such as by spacer 15, 115. Such a construction may be made by laminatingthe various layers together, in any suitable manner. Projection 30, 130,etc. may be formed on substrate(s) 12, 14, etc. before lamination, or,the overall shape of sensor strips 10, 110, etc. may be formed (e.g.,punched) after lamination of the various layers together. An alternatemethod for making sensor strips 10, 110, 210, 210′ and other sensors inaccordance with the invention, is to mold the sensors.

Molding may include positioning at least two spaced apart electricallyconductive electrodes (e.g., wires) in a mold, and molding a body ofinsulative material around the electrodes, with one end having thereinmeans for receiving a fluid sample. More specifically, molding couldinclude positioning at least two spaced apart electrically conductiveelectrodes (e.g., wires) in a mold, before or after molding, treating atleast one of the electrodes with one or more chemicals to change theelectrical properties of the treated electrode upon contact with a fluidsample, and molding a body of insulative material around the electrodeswith one end having therein means for receiving a fluid sample. The bodymay be molded in multiple pieces, e.g., two pieces, with a body and endcap for attaching to one another after the molding is completed, or in asingle piece.

A sensor may be made by positioning electrodes on one or moresubstrates, the substrates including a first substrate, optionallycontacting at least a portion of at least one electrode with sensingmaterial(s), and configuring the sensor by positioning a spacer betweenthe two substrates to maintain the substrates in a fixed, layeredorientation relative to each other.

Application of the Sensors

A common use for a sensor of the present invention, such as sensor strip10, 110, 210, 210′ is for the determination of analyte concentration ina biological fluid, such as glucose concentration in blood, interstitialfluid, and the like, in a patient or other user. Additional analytesthat may be determined include but are not limited to, for example,acetyl choline, amylase, bilirubin, cholesterol, chorionic gonadotropin,creatine kinase (e.g., CK-MB), creatine, DNA, fructosamine, glucose,glutamine, growth hormones, hormones, ketones, lactate, peroxide,prostate-specific antigen, prothrombin, RNA, thyroid stimulatinghormone, and troponin. The concentration of drugs, such as, for example,antibiotics (e.g., gentamicin, vancomycin, and the like), digitoxin,digoxin, drugs of abuse, theophylline, and warfarin, may also bedetermined.

Sensors may be available at pharmacies, hospitals, clinics, fromdoctors, and other sources of medical devices. Multiple sensors may bepackaged together and sold as a single unit; e.g., a package of about25, about 50, or about 100 sensors, or any other suitable number. A kitmay include one or more sensors, and additional components such ascontrol solutions and/or lancing device and/or meter, etc.

Sensors may be used for an electrochemical assay, or, for a photometrictest. Sensors are generally configured for use with an electrical meter,which may be connectable to various electronics. A meter may beavailable at generally the same locations as the sensors, and sometimesmay be packaged together with the sensors, e.g., as a kit.

Examples of suitable electronics connectable to the meter include a dataprocessing terminal, such as a personal computer (PC), a portablecomputer such as a laptop or a handheld device (e.g., personal digitalassistants (PDAs)), and the like. The electronics are configured fordata communication with the receiver via a wired or a wirelessconnection. Additionally, the electronics may further be connected to adata network (not shown) for storing, retrieving and updating datacorresponding to the detected glucose level of the user.

The various devices connected to the meter may wirelessly communicatewith a server device, e.g., using a common standard such as 802.11 orBluetooth RF protocol, or an IrDA infrared protocol. The server devicecould be another portable device, such as a Personal Digital Assistant(PDA) or notebook computer, or a larger device such as a desktopcomputer, appliance, etc. In some embodiments, the server device has adisplay, such as a liquid crystal display (LCD), as well as an inputdevice, such as buttons, a keyboard, mouse or touch-screen. With such anarrangement, the user can control the meter indirectly by interactingwith the user interface(s) of the server device, which in turn interactswith the meter across a wireless link.

The server device may also communicate with another device, such as forsending data from the meter and/or the service device to a data storageor computer. For example, the service device could send and/or receiveinstructions (e.g., an insulin pump protocol) from a health careprovider computer. Examples of such communications include a PDAsynching data with a personal computer (PC), a mobile phonecommunicating over a cellular network with a computer at the other end,or a household appliance communicating with a computer system at aphysician's office.

A lancing device or other mechanism to obtain a sample of biologicalfluid, e.g., blood, from the patient or user may also be available atgenerally the same locations as the sensors and the meter, and sometimesmay be packaged together with the sensor and/or meter, e.g., as a kit.

The sensors are particularly suited for inclusion in an integrateddevice, i.e., a device which has the sensor and a second element, suchas a meter or a lancing device, in the device. The integrated device maybe based on providing an electrochemical assay or a photometric assay.In some embodiments, sensors may be integrated with both a meter and alancing device. Having multiple elements together in one device reducesthe number of devices needed to obtain an analyte level and facilitatesthe sampling process. For example, embodiments may include a housingthat includes one or more of the sensor strips, a skin piercing elementand a processor for determining the concentration of an analyte in asample applied to the strip. A plurality of sensors may be retained in acassette in the housing interior and, upon actuation by a user, a singlesensor may be dispensed from the cassette so that at least a portionextends out of the housing for use.

Operation of the Sensor Strip

In use, a sample of biological fluid is provided into the sample chamberof the sensor, where the level of analyte is determined. The analysismay be based on providing an electrochemical assay or a photometricassay. In many embodiments, it is the level of glucose in blood that isdetermined. Also in many embodiments, the source of the biological fluidis a drop of blood drawn from a patient, e.g., after piercing thepatient's skin with a lancing device, which could be present in anintegrated device, together with the sensor strip.

After receipt of the sample in the sensor, the analyte in the sample is,e.g., electrooxidized or electroreduced, at the working electrode andthe level of current obtained at the counter electrode is correlated asanalyte concentration. The sensor may be operated with or withoutapplying a potential to the electrodes. In one embodiment, theelectrochemical reaction occurs spontaneously and a potential need notbe applied between the working electrode and the counter electrode. Inanother embodiment, a potential is applied between the working electrodeand the counter electrode.

The invention has been described with reference to various specific andpreferred embodiments and techniques. However, it will be apparent toone of ordinarily skill in the art that many variations andmodifications may be made while remaining within the spirit and scope ofthe invention. It is understood that elements or features present on oneembodiment described above could be used on other embodiments.

All patents and other references in this specification are indicative ofthe level of ordinary skill in the art to which this invention pertains.All patents and other references are herein incorporated by reference tothe same extent as if each individual patent or reference wasspecifically and individually incorporated by reference.

1-24. (canceled)
 25. A method of manufacturing a test strip, comprising:assembling said test strip having a test area including a testchemistry, said test area configured to collect a body fluid sample viacapillary action and analyze said body fluid sample, and cutting throughsaid test strip to form a first skin contacting tab and a second skincontacting tab after said assembling.
 26. The method of claim 25,wherein said assembling includes: disposing said test area onto either afirst panel or a second panel; and laminating said first panel to saidsecond panel.
 27. The method of claim 25, wherein said cutting includesstamping the test strip.
 28. The method of claim 25, wherein saidcutting includes cutting through said test area.
 29. A method ofmanufacturing a plurality of test strips, comprising: providing a firstpanel and a second panel wherein each of said first panel and saidsecond panel includes a continuous sheet of material; disposing a testarea having a reagent onto either said first panel or said second panel;assembling said first panel with said second panel; cutting through saidfirst panel and said second panel to form a plurality of test stripsafter said assembling; and cutting through said plurality of test stripsto form a first skin contacting tab and a second skin contacting tab foreach of said plurality of test strips.
 30. The method of claim 29,wherein said cutting includes cutting through said test area.